WO 2013/068552 and WO 2013/068554 disclose compounds which are known to have a dual muscarinic receptor antagonist and β2 adrenergic receptor agonist activity. However, many of these compounds cannot be formulated for effective delivery by inhalation as a dry powder which is challenging. It requires careful control of the particle size of the powder which is to be inhaled, and careful control of the particle size distribution. Further, it is important to avoid particle agglomeration or aggregation. In addition, when preparing pharmaceutical compositions and formulations for use in such devices, it is highly desirable to have a crystalline form of a therapeutic agent that is neither hygroscopic nor deliquescent and which has a relatively high melting point thereby allowing the material to be micronized without significant decomposition or loss of crystallinity.
Although the 2-amino-1-hydroxyethyl-8-hydroxyquinolin-2(1H)-one derivatives disclosed in WO 2013/068552 and WO 2013/068554 have shown adequate pharmacological behavior, it has proved difficult to obtain them in the form of a salt which is crystalline, not hygroscopic nor deliquescent and which has a relatively high melting point to enable micronization.
So far no crystalline salt of any of the compounds disclosed in WO 2013/068552 and WO 2013/068554 having the desired properties has been reported.
Accordingly, a need exists for stable, non-deliquescent salt forms of at least some of these compounds having acceptable levels of hygroscopicity and relatively high melting points.